Modern medicine supplies humanity with an unprecedented number and diversity of drugs, medicines, therapeutics, medicaments, treatments, and the like. A physician or health care provider may choose a drug or a combination of drugs and a most preferred means of delivery to the patient based upon several factors. The nature of the condition or disease and the overall state of health of the patient are two such exemplary factors. Additional examples include the type of medicine to be delivered, the therapeutic objective(s) to be achieved, the costs of the medicine and the available delivery options, and the time period in which the medicament must be administered to the target patient.
While selecting an appropriate course of treatment can be a challenging task, it is often only half of the battle. The physician must also choose a delivery method and system most suited to the particular ailment(s), the patient (whether it be an infant or incapacitated adult), the medicament to be delivered, and the time within which the medicine(s) must be received by the patient. Although each of these considerations are important in themselves, as those skilled in the art can appreciate, one of the most salient decisions facing the health care provider is the route of delivery.
The physician typically considers many variables before selecting a drug delivery route. Such factors include, for example, the target location in the body, the ease of administration, and the stability, solubility, miscibility, aerosolability, dispersability, and toxicity of the medicament and therapeutic agents. While considering these and other factors, the physician selects from delivery routes including needle injection to the veins, muscles, tissues, or cavities of the body; needle-free injection systems using pressurized gas; direct application to the dermis; direct application to a mucous membrane; inhalation or inspiration; and ingestion. Although these and other routes of drug delivery are possible, one of the more common routes of drug delivery for various physical anomalies is inhalation of aerosolized medicaments, which is used specifically for pulmonary and other types of respiratory ailments as well as where immediate non-vascular infusion of assimilable medicaments into the bloodstream is needed.
Inhalation-based drug delivery offers several advantages over other possible routes. One such advantage is that, since conscious patients can be very comfortable with inhaled medicaments, they can often medicate themselves easily and reliably by inspiring their desired medicines. Inhalation of therapeutics is therefore widely applicable to diverse patient populations. This issue is particularly important for long-term treatments and in treating infants and other patients with limited mobility, loss of fine motor control, or other incapacitation. A second advantage of inhaled medicine is the rapidity of drug dispersion throughout the body. If properly delivered to the highly vascularized pulmonary system of the lungs, and depending upon the medicament(s) to be administered, inhaled medicine can quickly enter the circulatory system via the pulmonary tract without the discomfort, invasiveness, risks of infection, or requisite skill associated with needle-based administration.
Furthermore, patients with collapsed, obscured, or otherwise difficult circulatory vessels can often benefit from inspiring their medicine. Not only can inhalation be easier for the patient, it can actually help to preserve the integrity of the therapeutic agent and prevent harm to possible distressed circulatory vessels. Further, an inhaled drug is not exposed to the harsh, acidic environment of the gastrointestinal tract. The conditions in the stomach can degrade, alter, or otherwise compromise many medicines, resulting in a potentially serious loss of efficacy. These same medicines may be stably delivered by inhalation, thereby preserving the anticipated function. Additionally, the potential discomfort to the patient and possible harm to the gastrointestinal tract resulting from use of medicaments known to have adverse effects thereupon can otherwise become a source of discomfort to the patient for myriad other reasons, can be sometimes avoided by inhalation treatment methods.
Yet another advantage of inhaled medicament therapeutics is the temporal flexibility of this method compared to ingestion. For example, physicians often warn patients to ingest their prescribed or preferred medicines either concurrently in time with mealtimes, and or with a specific food or a specific beverage, or without certain foods or beverages, or within a desired period of time proximate to such mealtimes or consumption of such specific foods or beverages. These admonitions and sometime requirements may force a patient to adjust their diet or other routines in order to accommodate their medication schedule, and this type of adjustment is often difficult if not impossible for the patient with child care and employment duties and other demands. Far more dangerous is the possibility that the patient will inappropriately take their medicine with or without such specific foods or beverages, or with the wrong type of food, or at the wrong time. Any of these scenarios might result in possible discomfort at best, and at worst potentially serious side effects, synergistic reactions, or a loss of drug efficacy. Depending upon the ailment being treated, the condition of the patient, and the proposed medicament(s), many of these considerations may not apply to inhaled medicines and corresponding treatment regimens.
In light of these and other advantages, it is unsurprising that inhalation is often the only, the best, or the preferred method of drug delivery. This can be especially true for pulmonary and respiratory related ailments wherein the medicament must be administered directly to the affected tissues immediately upon expression of particular symptoms. For example, asthmatic patients can experience distressing and sometimes fatal consequences resulting from asthmatic episodes that can have unknown origins or that can be triggered from foods, beverages, physical activity, exposure to various airborne substances or particles, or from exposure to stressful events. Such asthmatic individuals can significantly benefit from timely administered inhaled medicaments that can attenuate if not even completely avoid the more severe symptoms of asthma. One such effective medicament that is widely used in treating asthma and other ailments, and which is delivered via inhalation using any of a number of suitable devices is albuterol, which in 1994 was found to be the 14th most prescribed medicine of any kind by the National Center for Health Statistics, U.S. Dept. of Health and Human Services. Such proposed inhalation treatment regimens can often be very effective is ameliorating the symptoms quickly and without unduly undesirable side effects or other adverse consequences. And, such results can be accomplished with what are generally accepted to be relatively small doses of such medicaments. Those skilled in the art often refer to such small dosages as being in the range of approximately between 0.5 and 30 cubic centimeters or “CCs” (also referred to as milliliters wherein 1 milliliter is equal to 1 CC), and more preferably in the range of about 1 to 20 CCs, and even more preferably in the range of about 5 to 10 CCs. Other exemplary treatment substances and medicaments include inhalable antibiotics that can be useful in treating pseudomonas and related lung infections in Cystic Fibrosis patients.
Once a physician decides to administer this or another medicine via inspiration, several considerations remain. A first and fundamental consideration is to obtain the medicine in an inhalable form. Relatively few drugs are gaseous, and the process of sublimating or otherwise phase transitioning a liquid or solid drug to a gas can be costly, inefficient, can compromise or ruin the drug, or can be otherwise difficult or impossible. To overcome these difficulties, the most common approach to inhalation-based delivery is to disperse and suspend tiny droplets of a gas or a vapor or a liquid, or solid particles, of medicament in an airstream of ambient atmospheric air, some other gas such as oxygen or an artificial atmosphere, or some combination thereof, and then to deliver the dispersed suspension to the patient. Those with skill in the art may know this process as atomizing, aerosolizing, or nebulizing. A device that is used that incorporates this process is customarily known to those knowledgeable in the arts as an atomizer, a nebulizer, an aerosol dispenser, and more colloquially sometimes as an inhaler or a vaporizer.
Those skilled in the art employ many variations of nebulizers or atomizers and usually divide the various dispensing devices into 2 or more categories, which can be used in a variety of medical and industrial applications. For purposes of administering the small dosages known to be effective in treatment of various ailments to inhalation regimen treatments, those skilled in the art often refer to such nebulizers and atomizers as “small volume nebulizers,” among other commonly used phrases and names. In medical applications, further subcategories exist that classify such devices as to their intended disposable or reusable applications including, for example, devices that are compatible for use with the patient's own natural breathing rhythms, pressurized air ventilators such as those used in critical care environments, and intermittent positive pressure breathing equipment. A first type of device is a 2-phase system wherein the constituent medicine or substance to be dispensed in the nebulized or aerosolized air stream is mixed with either (1) a pressurized liquid propellant stream that expands into a gas upon release, (2) a pressurized gaseous propellant that expands into lower-pressure gas stream upon release, or some combination thereof. In this type of 2-phase system, various mechanical devices can be used in conjunction with the dispenser to further break up the now dispersed and suspended droplets or particles into even smaller droplets or particles. Other types of such dispensing devices include 3-phased and other multi-phased aerosol dispensers that can employ similar approaches wherein, for further example, the device incorporates a non-mixing liquified propellant with the proposed gaseous propellant, which are both dispensed with the constituent medicament or substance so as to further increase the dispersal of the constituent component in suspension in the dispensed nebulized or aerosolized air stream.
In the more common, present day drug delivery nebulizer devices and applications, those with skill in the art have made attempts to fabricate nebulizers and atomizers to have several functional components that can include, for purposes of illustrating various prior art devices, a base or reservoir for holding a substance or medicament to be dispensed, an air nozzle jet and capillary uptake feature that is adapted to disperse the substance into an airstream impinging upon a diffuser or baffle. The diffuser or baffle is usually designed for one or more capabilities. One capability is to break apart into smaller pieces the droplets or particles suspended in the incident airstream; another desirable function is to block large particles while passing particles or droplets that have been dispersed and atomized or nebulized into smaller particles or droplets having a maximum average diameter or size.
Such prior art attempts have been often touted to ideally atomize the dispersed substance into particles or droplets to have an average maximum diametrical dimension that is adapted either to be inhaled into the bronchial or to be inhaled into the even smaller alveoli airways in the lungs of the patient, or both. Atomization to obtain such desirable particle or droplet sizes has long been sought in the industry as has been noted in, for example, U.S. Pat. No. 3,762,409 to Lester, which recognized that droplets that are too small may be exhaled without effect and that droplets that are too large may be retained in the upper respiratory tracts without reaching the lower regions needing treatment) and U.S. Pat. No. 6,338,443 B1 to Piper, which noted that the most respirable droplet sizes are between 2 to 4 micrometers.
There have been many attempts at producing a variety of nebulizer and atomizer devices, all of which have demonstrated significant shortcomings and inefficiencies. Most notably among the problems in the prior art, it has been found that such devices usually produce unpredictable and widely varying results in terms of the efficiency of the dispensed aerosol substance. Such variations and uncertainty is pervasive in the industry without regard to manufacturer, device, or to the proposed approach, as may be illustrated in detailed descriptions of various U.S. patents, some of which are briefly described herein. Such unpredictability and variance has continued to plague the art and has thereby established a present and immediate need for improvement so that medical practitioners can achieve consistent and predictable results in prescribing aerosol-based treatment regimens that will have the anticipated and desired results.
One of the specific issues that persists in the prior art devices and that has received considerable attention in the prior art includes the difficulty in achieving desired particle or droplet sizes by fabricating such devices to have precise configurations and arrangements of elements between certain components so as to establish predictable atomization and nebulization of the substances to be dispensed in aerosol or atomized form. Another prevalent problem includes the inability of many of the prior art devices to utilize all of the substance to be dispensed that is received in the dispensing device. One additional especially notable problem in the art is that most of such devices must be used in a specific horizontal or vertical orientation, which depends upon the particular construction of the device. If not so used, the device will not operate as advertised to disperse, aerosolize, and dispense the treatment substance as expected, if at all.
One such prior art attempt is described in the U.S. Pat. No. 6,338,443 to Piper, which is limited to a high efficiency medical nebulizer that incorporates, among other elements, a housing that receives an intermediate section formed with various flow regulating orifices adapted to establish a jet spray, a lower liquid supply jar, an upper inhaler cap, an aerosol amplifier surface, and spray posts adapted to capture and prevent the release of droplets that are larger than desirable for the aerosol effluent. One of the various problems with the proposed '443 device that may be apparent to those knowledgeable in the relevant arts includes the unpredictability of the content of the substance to be dispensed in the effluent aerosol that is the result of the unpredictable distance that will be established between the amplifier surface and the orifices that create the spray.
Although many sources of unpredictability exist with the '443 Piper device, one of the more obvious sources of mostly uncontrollable variance exists in the fact that the manufacturing tolerances inherent in fabricating the inhaler cap and the integral amplifier surface, as well as the intermediate section, and the jar will result in an assembled device that multiplies the variance that exists in each of the components such that the distance between the amplifier surface and the jet spray orifices can be unacceptably misaligned or large or small. Since the distance between the amplifier surface and the orifices of the intermediate section cannot be reliably controlled during fabrication to an acceptable degree, at least without unusual and extraordinary manufacturing techniques, the resulting aerosol will necessarily contain an unpredictable amount of the substance that is to be dispensed in the effluent airstream. Additionally, in operation, it is likely that an untrained or inattentive user could easily improperly assemble the '443 device inducing even further misalignment and or establishing an undesired distance between the amplifier surface and the orifice, which would be compounded upon that already described above.
In further prior art attempts at addressing some of the problems of the prior art, U.S. Pat. Nos. 5,503,139 and 5,738,086, both to McMahon et al. teach, among other elements, the use of multiple individual components for the diffuser orifices and target baffles, which individual components are assembled after manufacture much in the same way as the Piper '443 device. These same problems were also evident in earlier proposed devices, including those described by Lester in U.S. Pat. No. 3,762,409 and suggested by Svoboda in U.S. Reissue Pat. No. RE 33,717. Other prior attempts amplify the inherent possible errors in establishing a critical distance between the jet creating diffuser orifice and the target baffle. In U.S. Pat. No. 5,533,497 to Ryder, among other features and design constraints, multiple components are required to be threadably assembled to establish the desired critical distance, which critical distance is specifically reliant upon complete threaded receipt of a housing component to a cap, which as already described, can have unexpected results in the hands of an unaware or untrained operator. In U.S. Pat. No. 4,657,007 to Carlin et al., another approach is suggested wherein certain components may be integrally formed via injection molding so as to improve manufacturability, among other purported advantages. However, even the Carlin et al. '007 device suffers from the same critical distance uncertainty problems rife in the present day technology in that the '007 device is limited to nebulizer having a separate friction fit-type cap and target component that must be properly seated on a conduit formed with the spray creating orifice so as to establish the desired atomization of the treatment substance. Here again, the Carlin et al. reference fails to appreciate the likelihood that the uncaring or unknowledgeable user will improperly seat the cap and target member so as to create the uncertain performance characteristics so common in the devices presently available on the market and known to those skilled in the art.
In addition to the difficulty or inability to precisely control the distances of import as noted above, many of these devices are also limited to embodiments having unnecessarily complicated effluent airstream pathways and that are restricted to difficult to manufacture constructions that often require expensive thermoplastic injection molds, all of which result in undesirable manufacturing challenges and increased production costs, as well as the inherent unpredictable performance characteristics.
The inconsistency and unpredictability of the noted approaches can be extremely wasteful, as many nebulizers are undoubtedly manufactured that do not produce particles of the desired size and that must therefore be rejected during post-manufacture inspection, if such is done. Additionally, since many of the prior art devices can have unpredictable performance during use, patients can be subject to under and over-medication, and the prescribed medication can be unavoidably wasted if underutilized by a dispenser device that is not properly aerosolizing and dispensing medicament or where such medicines are overused with the expectation that not enough medicament will be dispensed to the patient in light of the known problems with the prior art devices. The latter issues can be significantly costly for widely used medications that can often cost as much as $100 (See, for example, U.S. Pat. No. 5,738,086) or more per cubic centimeter (also referred to by those skilled in the arts as a “CC” or a milliliter, “mL”). Also, such problems can also result in difficulties for the patient who may use such a nebulizer thinking that medicine is being effectively delivered when in fact such delivery may be uncertain at best and completely absent at worst. The adverse consequences of such difficulty can be even more pronounced for infant or incapacitated patients unable to monitor the uptake of medicine into the effluent airstream of the nebulizer.
What has long been needed in the art is a small volume nebulizer that is easy and relatively inexpensive to manufacture, that both reduces the variability of particle size and is efficient, and that is still compatible with conventional methods of inspiration-based treatment. The present invention overcomes many of the problems prevalent in the prior art in a number of ways and with a wide range of contemplated embodiments, configurations, and alternative and preferred arrangements.